Carprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen, and ketoprofen. Carprofen reduces inflammation by inhibition of COX-2 and other sources of inflammatory biological targets. Carprofen has been approved by FDA as a veterinary drug for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain associated with soft tissue and orthopedic surgeries for dogs. Carprofen is supplied under the trade names Rimadyl, Novox, and Vetprofen in the dosages of 25 mg, 75 mg, and 100 mg of carprofen per tablet or caplet.
Carprofen is a white, crystalline compound. Carprofen is freely soluble in ethanol, but practically insoluble in water at 25° C. Carprofen is the nonproprietary designation for a substituted carbazole, 6-chloro-α-methyl-9H-carbazole-2-acetic acid. The empirical formula is C15H12ClNO2 and the molecular weight 273.72. The chemical structure of carprofen is:

The synthesis of carprofen was first reported in 1970s by a group of scientists at Hoffmann-La Roche Inc. in U.S. Pat. No. 4,158,007. According to the patent, carprofen can be prepared by using cyclohexenone and 2-methylmalonate as starting materials, as summarized below:

The starting material, cyclohexenone, is expensive. As a reference point, Sigma-Aldrich sells it at $120.50 per 0.1 liter. Consequently, the above process is not suitable for the manufacture of carprofen on an industrial scale.
Scientists at Hoffmann-La Roche Inc. later reported what they thought a better process to prepare carprofen in EP 0,151,423 by starting from carbazole, as summarized below:

However, the process is also not suitable for industrial manufacturing because it requires the use of toxic trimethylsilyl cyanide as a reagent and it forms isomers during the chlorination step and the subsequent step. Additionally, carbazole is an expensive starting material, currently sold at a price of $111.50 per 0.2 gram at Sigma-Aldrich.
Thereafter, scientists at Hoffmann-La Roche reported a different, improved chemical process to make carprofen and its derivatives, again starting from carbazole, in EP 0,247,222.

The above chemical process eliminates the need to use toxic trimethylsilyl cyanide. The chemical process was further optimized by a group of Chinese scientists, as reported in CN 101492412. Nevertheless, the chemical process is still not ideal because the chlorination step therein is too complicated because it requires region-selective chlorination at two specific sites of the molecule.
A few other synthetic routes to prepare carprofen were reported in U.S. Pat. Nos. 4,150,031 and 4,264,500. Again, they use carbazole or a derivative thereof as a starting material. For example, U.S. Pat. No. 4,150,031 discloses that:

The lengthy synthetic steps and stringent reaction conditions of the above process make it unsuitable for a large scale production.
WO 87/00519 discloses a process of making carprofen starting from 7-chloro-3-bromocarbazole via a coupling reaction and an oxidation reaction as shown below:

This process is not practical for industrial manufacturing of carprofen because the starting material, 7-chloro-3-bromocarbazole, itself requires multiple-step synthesis.
Therefore, there is a need in the industry to provide an economical, efficient and viable process for the preparation of carprofen that is suitable for industrial scale manufacturing.